AUTHOR=Hickey Ana , Stamou Panagiota , Udayan Sreeram , Ramón-Vázquez Ana , Esteban-Torres Maria , Bottacini Francesca , Woznicki Jerzy Adam , Hughes Owen , Melgar Silvia , Ventura Marco , Van Sinderen Douwe , Rossini Valerio , Nally Ken 

TITLE=Bifidobacterium breve Exopolysaccharide Blocks Dendritic Cell Maturation and Activation of CD4+ T Cells

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.653587

DOI=10.3389/fmicb.2021.653587

ISSN=1664-302X

ABSTRACT=<p>Exopolysaccharide (EPS) is a bacterial extracellular carbohydrate moiety which has been associated with immunomodulatory activity and host protective effects of several gut commensal bacteria. <italic>Bifidobacterium breve</italic> are early colonizers of the human gastrointestinal tract (GIT) but the role of EPS in mediating their effects on the host has not been investigated for many strains. Here, we characterized EPS production by a panel of human <italic>B. breve</italic> isolates and investigated the effect of EPS status on host immune responses using human and murine cell culture-based assay systems. We report that <italic>B. breve</italic> EPS production is heterogenous across strains and that immune responses in human THP-1 monocytes are strain-specific, but not EPS status-specific. Using wild type and isogenic EPS deficient mutants of <italic>B. breve</italic> strains UCC2003 and JCM7017 we show that EPS had strain-specific divergent effects on cytokine responses from murine bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs). The <italic>B. breve</italic> UCC2003 EPS negative (EPS<sup>–</sup>) strain increased expression of cytokine genes (<italic>Tnfa, Il6, Il12a</italic>, and <italic>Il23a</italic>) relative to untreated BMDCs and BMDCs treated with wild type strain. <italic>B. breve</italic> UCC2003 and JCM7017 EPS<sup>–</sup> strains increased expression of dendritic cell (DC) activation and maturation marker genes (<italic>Cd80, Cd83</italic>, and <italic>Cd86</italic>) relative to untreated BMDCs. Consistent with this, BMDCs co-cultured with <italic>B. breve</italic> UCC2003 and JCM7017 EPS<sup>–</sup> strains engineered to express OVA antigen activated OVA-specific OT-II CD4<sup>+</sup> T-cells in a co-culture antigen-presentation assay while EPS proficient strains did not. Collectively, these data indicate that <italic>B. breve</italic> EPS proficient strains use EPS to prevent maturation of DCs and activation of antigen specific CD4<sup>+</sup> T cells responses to <italic>B. breve</italic>. This study identifies a new immunomodulatory role for <italic>B. breve</italic> EPS and suggests it may be important for immune evasion of adaptive immunity by <italic>B. breve</italic> and contribute to host-microbe mutualism.</p>